促红细胞生成素对大鼠肾脏缺血再灌注损伤的抗炎保护作用及其机制  

Protective effect of erythropoietin on inflammation of renal ischemia-reperfusion injury in rats

作　　者：汪悠悠[1] 贾宁[1] 彭莉[1,2] 张慧涛[1] 朱晔[1] 郑晶[1] 朱伟平[1] 张桦[1] 

机构地区：[1]中山大学附属第五医院肾内科,广东珠海519000 [2]澳门镜湖医院

出　　处：《中华临床医师杂志（电子版）》2013年第19期78-81,共4页Chinese Journal of Clinicians(Electronic Edition)

基　　金：珠海市科技计划项目(PC20071009)

摘　　要：目的探讨促红细胞生成素(EPO)对大鼠肾脏缺血再灌注损伤(IRI)的抗炎保护作用及其机制。方法 36只雄性SD大鼠随机分为假手术(SOR)组、IRI组和EPO组,每组12只。于再灌注2 h、6 h、12 h、24 h各时相点观察肾脏病理改变,检测血尿素氮(BUN)和肌酐(Scr)水平,ELISA法检测肾组织匀浆肿瘤坏死因子-α(TNF-α)含量,Western印迹法检测磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)蛋白表达。结果 IRI组血BUN、Scr水平和肾组织匀浆TNF-α含量显著升高,并出现明显的肾脏病理改变;肾组织p-p38MAPK蛋白表达明显增强,于再灌注12 h达到峰值,24 h表达减弱。而在EPO组,BUN、Scr和TNF-α水平显著低于IRI组(P<0.05),在各时相点的肾脏病理改变与同期IRI组比较明显减轻,p-p38MAPK表达在各时相点较IRI组明显减弱。结论 EPO可显著改善IRI造成的肾脏病理和肾功能异常,其肾脏保护作用可能与抑制p38MAPK活化、降低TNF-α水平、减轻炎性损伤有关。Objective To investigate protective effects and mechanisms of erythropoietin （EPO） on inflammation induced by renal ischemia-reperfusion injury （IRI） in rats. Methods A total of 36 male Sprague-Dawley rats were randomly divided into 3 groups of Sham operation （SOR）, IRI and EPO pretrealnaent （n= 12 in each group）. Renal IRI model was created by clamping the bilateral renal pedicle for 45 min and then released. 3000 IU/kg of EPO was administered in EPO group via the abdominal cavity 24 hours before clamping. Blood samples and the kidney were obtained at 2, 6, 12 and 24 h after reperfusion. The. serous concentrations of blood urea nitrogen and serum creatinine were measured.The levels of tumor necrosis factor a （TNF-a） in the renal tissues were detected by ELISA, and the expression of phosphorylating-p38 mitogen-activated protein kinase （p-p38MAPK） in the renal tissues were assessed by western blot analyses. Results Compared with IRI group, the EPO treated group exhibited lower serum urea and creatinine levels（P〈0.05） and limited the renal histopathological lesion. The concentration of TNF-a and the expression of p-p38MAPK in renal tissue were greatly increased by IRI, but significantly reduced by the treatment of EPO. Conclusion EPO can attenuate the renal injury and dysfunction caused by IRI via reducing the expression of p-p38MAPK and the production of TNF-a. The renoprotective effect of EPO might be mediated by its inhibition of inflammation.

关 键 词：再灌注损伤 红细胞生成素 P38丝裂原活化蛋白激酶类 肿瘤坏死因子A 

分 类 号：R692[医药卫生—泌尿科学]